Background: Atherosclerosis is a chronic pathological condition that has remained clinically silent for decades, and the epidemic has continued to be on the rise due to risk factors, including diet, lifestyle, hyperlipidemia, pathogenic microorganisms, and aging. Using various synthetic drugs in treating atherosclerosis is associated with a high risk of myositis, angioedema, myoglobinuria, and acute renal failure. Various side effects of the available drugs have been reported; attempts are underway to explore natural sources with antiatherosclerotic activity. Aim and objective: Using a diet-induced atherosclerosis rat model, the current study tested the hypothesis of antiatherosclerotic and antihyperlipidemic roles of Terminalia catappa fruit extracts. Materials and Methods: Atherosclerosis in Wistar rats was induced using an atherogenic diet. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), creatine kinase (CK), and lactate dehydrogenase (LDH) were determined using analytical kits. Results: Quantitative phytochemical analysis of the extracts demonstrated that the plant had flavonoids, saponins, tannins, terpenoids, alkaloids, cardiac glycosides, sterols, phenols, and anthraquinones. Diet-induced atherogenic Wistar rats showed a significant (p < 0.05) increase in total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol compared to the healthy control group; however, the atherogenic lipid profile was reversed by the treatment of T. catappa fruit extracts. The biochemical experiments demonstrate that T. catappa fruit extracts have an antihyperlipidaemic effect, shown by a decreased coronary risk index and the atherogenic index, and an increased cardioprotective index, compared to disease control. Conclusion: The current study indicates that T. catappa fruit extracts may contain bioactive molecules to treat atherosclerosis.

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